PROJECT SUMMARY/ABSTRACT Men who have sex with men (MSM) in the United States (US) remain disproportionately burdened by HIV and bacterial sexually transmitted infections (STIs), such as gonorrhea, chlamydia and syphilis. Comprehensive HIV prevention efforts have been increasingly focusing on biomedical strategies, such as pre-exposure prophylaxis (PrEP). Testing is the first step in offering PrEP for HIV prevention to those who test negative, or initiating treatment for HIV and bacterial STIs among those who test positive. However, testing levels among MSM in the US are suboptimal due to multiple barriers such as concerns regarding stigma, privacy and confidentiality, lack of transportation, insufficient clinic time and limited access to healthcare. PrEP relies on adequate adherence to be effective in real world settings, and adherence biomarkers need to be incorporated into PrEP implementation and roll-out programs for MSM. Self-collection of biological specimens at home and their return by mail for lab testing might be a resource-efficient strategy to increase the rates of testing for HIV and bacterial STIs among young, high-risk MSM, and to ensure adherence among those on PrEP. Most research on specimen self-collection has focused on self-collection in a clinic, with its immediate return to clinic staff for subsequent testing. Little information is available regarding the acceptability and feasibility of self-collecting and returning different types of biological specimens by mail for HIV and bacterial STI testing, or for potential PrEP adherence monitoring. Data on which types of specimens MSM are willing to self-collect at home, which ones they actually mail back, and finally, the adequacy of returned specimens for lab testing, are essential for designing effective testing interventions and remote monitoring strategies targeting this risk group. To fill these significant knowledge gaps, we propose to conduct a novel mixed methods study, guided by the Information-Motivation-Behavioral skills model, to explore the acceptability and feasibility of self-collecting at home and returning by mail all, some, or none of five different biological specimens among 100 high-risk, HIV-negative or unknown status MSM (18-34 years, 50 black and 50 white) recruited through social media. In Phase 1, we will send participants a box containing instructions and materials for self-collecting and potentially returning a dried blood spot (for actual HIV and potential syphilis testing), pharyngeal, urethral, and rectal swabs (for actual gonorrhea and chlamydia testing), and a hair sample (for potential PrEP adherence monitoring). HIV, gonorrhea, and chlamydia test results will be returned back to participants by trained counselors over the phone, and men who test positive will be linked to local healthcare services. In Phase 2, we will conduct individual in-depth interviews using VSee, a video-based teleconferencing software, with 32 participants: 16 (8 black, 8 white) who returned all five specimens, and 16 (8 black, 8 white) who returned some or no specimens. Our results will provide formative data which can be used to plan HIV and bacterial STI prevention programs and remote PrEP monitoring strategies for other sexual and gender minorities at risk, such as transgender men and women, as well as cisgender women.